Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. A 58-year-old woman was treated with everolimus as a third-line therapy for metastatic clear-cell renal carcinoma. She was given oral everolimus 10 mg once daily. During the fourth week of her first cycle, the patient was admitted to our hospital because of an acute-onset, right upper quadrant pain associated with nausea and vomiting. She was diagnosed with acute cholecystitis, which was treated with broad-spectrum antibiotics, and everolimus therapy was discontinued. A follow-up computed tomography scan of the abdomen revealed a complete resolution of gallbladder changes. Our patient did not have major risk factors for developing a cholecystitis except for a relative immunosuppressed state secondary to her advanced renal cancer. The Naranjo adverse drug reaction probability scale score for this event was 5, indicating a probable association of the event with everolimus. Because the use of everolimus is expanding in clinical practice, we want to alert the oncology community about this uncommon and life-threatening complication in patients receiving everolimus or another agent with antiangiogenic activity. To our best knowledge, only one case of an acute cholangitis associated with everolimus in a metastatic renal cell carcinoma has been reported. We report herein the first case of a metastatic renal cell carcinoma developed everolimus-associated cholecystitis that was completely reversed after drug withdrawal.